Dystonia and Cerebellum : From Bench to Bedside

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using various dystonia rodent models and clinical studies in dystonia patients continues to provide new pieces of knowledge regarding the role of the cerebellum in dystonia genesis. Herein, we review basic and clinical articles related to dystonia focusing on the cerebellum, and clarify the current understanding of the role of the cerebellum in dystonia pathogenesis. Given the recent evidence providing new hypotheses regarding dystonia pathogenesis, we discuss how the current evidence answers the unsolved clinical questions

A Keck/DEIMOS Spectroscopy of Lyman Alpha Blobs at Redshift z=3.1

We present the results of an intermediate resolution (~2 angstrom) spectroscopy of a sample of 37 candidate Lyman alpha blobs and emitters at redshift z=3.1 using the DEIMOS spectrograph on the 10 m Keck telescope. The emission lines are detected for all the 37 objects and have variety in their line profiles. The Lyman alpha velocity widths (FWHM) of the 28 objects with higher quality spectra, measured by fitting a single Gaussian profile, are in the range of 150 - 1700 km/s and correlate with the Lyman alpha spatial extents. All the 12 Lyman alpha blobs (>16 arcsec^2) have large velocity widths of > 500 km/s. While there are several possible physical interpretations of the Lyman alpha velocity widths (motion of gravitationally-bound gas clouds, inflows, merging of clumps, or outflows from superwinds), the large velocity widths of the Lyman alpha blobs suggest that they are the sites of massive galaxy formation. If we assume gravitationally-bound gas clouds, the dynamical masses of the Lyman alpha blobs are estimated to be ~10^12 - 10^13 Msun. Even for the case of outflows, the outflow velocities are likely to be the same order of the rotation velocities as inferred from the observational evidence for local starburst galaxies.Comment: Accepted for publication in ApJ

Effect of a Rehabilitation Program After Mesenchymal Stromal Cell Transplantation for Advanced Osteonecrosis of the Femoral Head: A 10-Year Follow-Up Study

Objective: To assess the status of 10 patients with advanced osteonecrosis of the femoral head who underwent mesenchymal stromal cell transplants and a 12-week rehabilitation program 10 years earlier. Design: Retrospective study. Setting: University clinical research laboratory. Participants: Patients (N=10) who had undergone mesenchymal stromal cell transplantation and rehabilitation for a single hip osteonecrosis of the femoral head 10 years prior to the current study were recruited by telephone. The average age was 31.7 years and all participants were men; radiographic stages were 3A in 6 patients and 3B in 4 patients before treatment. Intervention: A 12-week rehabilitation program with follow-up once every 1 to 2 years was performed after mesenchymal stromal cell transplantation. Main Outcome Measures: Radiographic analysis, clinical score, timed Up and Go test, hip function (range of motion, muscle strength), and Short Form-36 scores were assessed before treatment and 1 and 10 years after treatment. Results: Upon imaging, 5 hips were found to be stable (stable group) and 5 had progressed (progressed group); 2 of the latter group required a total hip arthroplasty. The pretreatment radiographic stage of the progressed group was more advanced than that of the stable group. Body mass index was higher in the progressed group than in the stable group. Hip function and clinical score at 1 and 10 years after treatment improved in the hips of 8 patients without total hip arthroplasty. There were no severe adverse events during the rehabilitation. Conclusions: The 12-week rehabilitation program and annual follow-up after mesenchymal stromal cell transplantation for osteonecrosis of the femoral head was associated with pain reduction, maintaining hip muscle strength, widening range of motion, and improving quality of life. The level and timing of weight-bearing and social activity should be planned according to the individual's lifestyle and body composition

L-Qモデルは転移性脳腫瘍の定位放射線照射に適用可能か?

The biologically effective dose (BED) based on the linear-quadratic (LQ) model has been commonly used to evaluate the dose-effect relationships among the different fractionation schedules, but whether the LQ model is appropriate for hypofractionated (HF) high-dose stereotactic irradiation (STI) is uncertain. The validity of the model at high doses per fraction has been critically examined. In this study, STI of metastatic brain tumors was evaluated to suggest the applicability of the LQ model to HF high-dose radiotherapy. No significant difference was found between stereotactic radiosurgery (SRS) and HF stereotactic radiotherapy (SRT) in the analyses of 151 tumors. Furthermore, no significant differences were found among SRS, HF-SRT, and non-HF SRT in 117 metastatic lung adenocarcinomas. The results of this study suggest that BED calculation is a reasonable approach for careful dose-effect evaluation based on the LQ model for HF high-dose radiotherapy for metastatic brain tumors, especially lung adenocarcinomas.博士（医学）・甲第688号・平成30年9月26

A First View of the Effect of a Trial of Early Mobilization on the Muscle Strength and Activities of Daily Living in Mechanically Ventilated Patients With COVID-19

Objective: To retrospectively investigate the effect of early mobilization on the muscle strength and activities of daily living in patients with COVID-19 under mechanical ventilation. Design: This was a single-center, retrospective, observational study. Setting: Inpatient rehabilitation care in Japan. Participants: The study subjects were divided based on the onset of mobilization: under mechanical ventilation (n=17; aged 68.5±11.9, 13 male) and after extubation (n=11; aged 59.7±7.1, 6 male; N=28). Interventions: Mobilization, including dangle sitting, standing, walking, and muscle strengthening exercises. Main Outcome Measures: The outcome measures were Barthel Index, Medical Research Council Manual Muscle Test, and intensive care unit Mobility Scale. Results: The difference in the Barthel Index, Medical Research Council Manual Muscle Test, and intensive care unit Mobility Scale scores pre- and postintervention were not statistically significant between the 2 groups, but all significantly improved after the intervention. Conclusion: This small sample size study found no difference in the functional recovery of patients with severe COVID-19 who underwent early mobilization under mechanical ventilation relative to when it was begun after extubation

Large-scale Filamentary Structure around the Protocluster at Redshift z=3.1

We report the discovery of a large-scale coherent filamentary structure of Lyman alpha emitters in a redshift space at z=3.1. We carried out spectroscopic observations to map the three dimensional structure of the belt-like feature of the Lyman alpha emitters discovered by our previous narrow-band imaging observations centered on the protocluster at z=3.1. The feature was found to consist of at least three physical filaments connecting with each other. The result is in qualitative agreement with the prediction of the 'biased' galaxy-formation theories that galaxies preferentially formed in large-scale filamentary or sheet-like mass overdensities in the early Universe. We also found that the two known giant Lyman alpha emission-line nebulae showing high star-formation activities are located near the intersection of these filaments, which presumably evolves into a massive cluster of galaxies in the local Universe. This may suggest that massive galaxy formation occurs at the characteristic place in the surrounding large-scale structure at high redshift.Comment: 11 pages, 3 figures, accepted for publication in ApJ Letter

Biological Dose Evaluation Of Radiotherapy By Equivalent Dose In 2Gy Fractions (EQD2) In Recurrent Glioblastoma.

The standard treatment for glioblastoma is surgery followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. A total dose of 60 Gy given in 2 Gy fractions (fr) with concurrent and adjuvant TMZ has been recommended; however, local recurrences are frequent and the prognosis remains very poor. In this study, the equivalent dose in 2Gy fr (EQD2) at the recurrent site of glioblastoma was assessed to evaluate the biological effect of RT on glioblastoma considering that α/β ratios might vary from 1 to 10 Gy. Recurrences were found in gross tumor volume (GTV) areas in all 11 patients, and 8 of them also showed recurrence in clinical target volume (CTV). Differences in EQD2 according to α/β ratios were relatively small in high-dose areas around 60 Gy; however, low-dose areas often showed significant differences of EQD2 according to the α/β ratios. In patients that received 60 Gy in 2 Gy fr, EQD2 was less than the original physical dose and became smaller as the α/β ratio became smaller. The comparison of the dose distribution of EQD2 and dose volume histogram (DVH) of EQD2 between α/β ratios 1 and 10 suggested that little difference was found in relatively high-dose areas but a significant difference was found in low-dose areas. In contrast, if the fraction size was larger than 2 Gy, EQD2 was greater than the original physical dose and it became larger as the α/β ratio became smaller. In conclusion, this study showed that the standard RT 60 Gy in 2 Gy fr is insufficient for glioblastoma, and it suggested that biological effects might differ significantly according to each fraction size of radiation and α/β ratio of the linear quadratic (LQ) model